The goal of this project to fully understand the genetics of certain inherited behaviors segregating in specific strains of silver foxes. The range of behaviors in these foxes has significant parallels to that of normal and disordered patterns of human sociability. The proposed research will characterize the genetic loci determining fox behavioral phenotypes to yield insights into the genetics of social behavior and its underlying molecular mechanisms, not only in foxes, but in other mammals, including humans. In previous studies, specific strains of silver fox (Vulpes vulpes) were developed, at the Russian Institute of Cytology and Genetics (ICG), that exhibit extremely friendly behavior towards humans, in contrast to their wild-type ancestors that resist human contact. The current proposal is a joint research project between scientists at Cornell University, ICG, and the University of Utah, to define the molecular genetic mechanisms underlying these different behaviors. Fox behavioral phenotypes have been defined using principal-components analysis. Genetic loci underlying these behavioral phenotypes have been mapped in powerful sets of fox backcross pedigrees using the newly developed meiotic linkage map of the fox genome. These identified quantitative trait loci will be validated in extended sets of highly informative experimental pedigrees. Combined linkage and linkage disequilibrium mapping will be applied to define the critical regions of the fox genome in which quantitative trait loci have been identified, and identify potential candidate genes. The effect of identified loci on behavior will be determined in experimental pedigrees using marker assisted selection. The identification of genes and loci influencing social behavior in foxes is anticipated to provide new insights into, and candidate genes for human disorders of social behavior. Furthermore, such a well- established large animal model, intermediate between rodents and primates in biological complexity, would then offer opportunities to investigate potential therapies for such human disorders as autism, schizophrenia, anxiety, depression, personality disorders, panic disorder and other traits.